An in vitro model using renal cortical slices has been developed to evaluate acutely-acting proximal tubular nephrotoxicants. The toxicity of several classifcal nephrotoxicants (including HgC12, D2Cr207, CC14, hexachlorobutadiene, cephaloridine, gentamicin and 4-ipomeanol) has been evaluated in this system using Fischer 344 rat kidney. Conditions have been established where several physiologic parameters can be monitored after a single incubation of 100 mg renal cortical slices. Although the data for in vitro slice exposure appear to coorelate well with in vivo nephrotoxicity, quantitative comparisons between different nephrotoxicants are probably inappropriate. Thus, this model will not be useful for routine screening of unknown compounds. Nevertheless, there are similarities in the characteristics of nephrotoxicity observed in vitro and those reported in vivo, suggesting the model may be useful for mechanistic evaluations of certain classes of nephrotoxicants. Preliminary data suggest this model may be of particular use in evaluating nephrotoxicity of platinum anticancer drugs.